Microbiota in mesenteric adipose tissue from Crohn's disease promote colitis in mice

Zhen He1,2, Jinjie Wu1,2, Junli Gong1,2

  • 1Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.

Microbiome
|November 24, 2021
PubMed
Abstract

Insights

Mesenteric resident bacteria in Crohn's disease (CD) patients promote intestinal inflammation. The bacterium Achromobacter pulmonis was found to exacerbate colitis in mouse models, suggesting a role in CD pathogenesis.

Area of Science:

  • Gastroenterology
  • Microbiology
  • Immunology

Background:

  • Crohn's disease (CD) is characterized by mesenteric adipose tissue (mAT) hyperplasia, termed creeping fat.
  • The prognostic significance of creeping fat in CD surgery is known, but the underlying mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of mesenteric microbiota in the pathogenesis of Crohn's disease.
  • To identify specific bacteria within mAT that contribute to intestinal inflammation.

Main Methods:

  • Integrated analysis of mesenteric microbiome, metabolome, and host transcriptome in CD patients and controls.
  • 16S rRNA sequencing, host RNA sequencing, and metabolomics were employed.
  • Isolation and functional validation of mAT resident bacteria in mouse colitis models (DSS and Il10-/-).

Main Results:

  • Mesenteric microbiota in CD patients contribute to aberrant metabolites and transcripts in mAT.
  • The presence of mAT resident microbiota is linked to CD development.
  • Achromobacter pulmonis (A. pulmonis) isolated from CD mAT translocated and worsened colitis in mice, with higher levels observed in CD patients.

Conclusions:

  • Mesenteric microbiota in CD patients create a harmful microenvironment that promotes intestinal inflammation.
  • A. pulmonis may play a significant role in the inflammatory processes of Crohn's disease.